Opioids II Flashcards
What are the patterns of use of opioids?
- many users are chippers –> occasional use (this proves that people do not become instantly addicted)
- there are also “needle freaks” which are people who associate IV injection with the drug and start to enjoy the act of the injection almost more than the drug itself and can do harmful things like start injecting themselves with any fluid to get high
- true addicts use min. once daily to 20 or more times a day
can be expensive up to $600 a day or more which is why people resort to crime when they have these addictions
only 10-15% of people who try opioids will have potential for long term addiction
What are the four distinct families of endogenous opioid-like substances and their receptors? And what are their functions?
- enkephalins (delta)
- endorphins (mu)
- endorphins (mu)
- dynorphins (kappa)
each family is derived from different precursor proteins
- all contain tyrosine at their N-terminus
- parts of the morphine mimic the tyrosine which is an amino group separated from a phenyl ring by two carbons
- it may function as NT, neurohormones or neuromodulators
- involved in pain, placebo response, acute stress responses and social attachment
What are the different (3) types of opioid receptors?
mu: euphoria, respiratory depression, analgesia, dependence. –> has a large open binding pocket that may allow for rapid exchange of ligands
delta: some analgesic effects
kappa: dysphoria, negative effects, some analegsic effects
for the mu receptor: the binding site is buried in the middle with the opiod attached to it. Usually receptor pockets close when bound to agnostic but in Mu receptor case, it doesn’t and its wide open, so when you give an antidote, it has a rapid effect because it has access to the binding pocket and can compete with the agnoist
What happens to neurotransmitter release when opiod receptors are activated?
they inhibit all adenyl cyclase and reduce cAMP levels
opioids tend to decrease neuronal excitability at the cellularr level which is why they are so good at interrupting pain signals
in the reward pathway, they increase dopamine release in the NA by inhibiting inhibition
What happens presynaptically when opioids bind to their receptors?
inhibit nT release by inhibiting calcium influx via inhibition of the opening of mostly N-type voltage gated calcium channels
What happens postynaptically when opioids bind to their receptors?
hyperpolarizsation of the membrane by enhancing K+ flow outwards by stimulating the opening of specific potassium channels
How does the VTA to NA pathway works without presence of opioids?
in the absence of opioids, GABA is released from one presynaptic terminal
it binds to GABA-A receptor on different presynaptic terminal
this has an inhibitory effect NT (dopamine release)
How does the VTA to NA pathway works in the presence of opioids?
when opipods are present they bind to presynaptic receptors which has an inhibitory effect on GABA release
therefore less GAAB binds to the GABA-A receptor on the adjacent nerve ending
net result is that more dopamine is released
more activation of postsynaptic dopamine receptors
What is the relationship between opioids and dopamine release?
small changes in dopamine levels in the NA in animals which shows less addictive properties??
morphine produces the same change in dopamine levels as nicotine
heroin users have claimed that quitting cigarettes was as difficult or even more so
Nutt’s paper proposes that dopamine is only important for the craving of opioids but not for the reward or euphoria
How does tolerance develop in opioid users?
develops to analgesia, vomitting, euphoria, and respiratory. depression
constipation and pupil constriction affected very little
addicts can take as much as 50 times the normal analgesic dose of morphine with little respiratory depression which can lead to problems if they stop using for a period of time, lose tolerance and then resume with same dose (i.e. rehab can cause OD’s)
What are the mechanisms of tolerance?
some mu receptors internalize to acute use
loss of effect of activated receptor on cAMP levels –> activated receptors no longer inhibits adenyl cyclase
long term receptor down regulation but not always shown to be part of tolerance
up regulation of the neurotransmitter receptors and effects on neurogenesis and neuronal structure
What kind of damage can heroine cause?
many studies have found no major damage to organs of heroin users
most damage is due to poor nutrition, adulterated (impure drugs), infections from needles (hepatitis, HIV), concomitant drug use and general lifestlye
analgesic effects mask pain of infections or problems
What happens in the case of a overdose (3 things)?
Opioid overdose “triad”:
- coma
- depressed respiration
- pinpoint pupils
death from respiratory depression
What can cause overdose in opioid addicts?
- can happen when thees a new supplier, and heroin goes from being impure to suddenly more pure and the same dose you took before can have more heroin in it …or it can be adulterated with fentanyl or other substances that can kill you
- environment and changing environment plays a role
- having undergone treatment, lost tolerance and then took same dose
- in one study of overdose patients:
85% of them had a depressant
45% of those depressants were benzodiazepines
36% had alcohol
most OD’s occur in combination with other drugs
What is naloxone? how does it prevent overdose?
naloxone is a fast acting opiod antagonist but only lasts 20-30 minutes
can reverse the opioid induced respiratory depression, coma and mitosis and prevent death if given within minurtes of the overdose
